Some of the more important positive feedback mechanisms that are evident during hemorrhage include (1) cardiac failure, (2) acidosis, (3) central nervous system depression, (4) aberrations in blood clotting, and (5) depression of the mononuclear phagocytic system (MPS).
These mechanisms are discussed next.
Shifts to the right in ventricular function curves, particularly in the later stages of hemorrhagic shock (
Fig. 19.24 ), provide evidence of a progressive depression in myocardial contractility during hemorrhage.
*The MPS (previously called the reticuloendothelial system) consists of macrophages that are distributed throughout the body. They are derived from bone marrow and exist for a short period in circulating blood as monocytes. They then migrate into tissues, where they phagocytose foreign material and present antigens to lymphocytes to initiate the adaptive immune response. Cells of the MPS include the Kupffer cells of the liver, alveolar macrophages, microglia, and Langerhans cells.
•Fig. 19.24 Ventricular Function Curves for the Left Ventricle During the Course of Hemorrhagic Shock. Curve A representsthecontrolfunctioncurve;curves B toF representtimeafterthehemor-rhage:117minutes(curve B), 247minutes(curve C), 280minutes(curve D), 295minutes(curve E), and310minutes(curve F). (RedrawnfromCrowellJW,GuytonAC.Am J Physiol. 1962;203:248.)–2 0 2 4 6 8 10 12 0 200 400 600 800 1000 1200 1400 1600 A E F C D B Left atrial pressure (mm Hg) Cardiac output (mL/min)
The hypotension induced by hemorrhage reduces coronary blood flow and therefore depresses ventricular function. The consequent reduction in cardiac output further reduces arterial pressure, a classic example of a positive feedback mechanism. Furthermore, reduced blood flow to peripheral tissues leads to an accumulation of vasodilator metabolites that decrease peripheral resistance and therefore aggravate the fall in arterial pressure.
The inadequate blood flow during hemorrhage affects the metabolism of all cells. The decreased O2 delivery to cells accelerates tissue production of lactic acid and other acid metabolites. Moreover, impaired kidney function prevents adequate excretion of the excess H+ , and generalized metabolic acidosis ensues. The resulting depressant effect of acidosis on the heart is a further reduction in tissue perfusion, which aggravates the metabolic acidosis. Acidosis also reduces the reactivity of the heart and resistance vessels to neurally released and circulating catecholamines and thereby intensifies the hypotension.
The hypotension in shock reduces cerebral blood flow. Moderate degrees of cerebral ischemia induce pronounced sympathetic nervous stimulation of the heart, arterioles, and veins, as noted earlier. In severe hypotension, however, the cardiovascular centers in the brainstem eventually become depressed because of inadequate cerebral blood flow. The resulting loss of sympathetic tone then reduces cardiac output and peripheral resistance. The consequent reduction in Pa intensifies the inadequate cerebral perfusion.